Category Archives: Addiction

The dopamine theory of addiction: 40 years of highs and lows.

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“For several decades, addiction has come to be viewed as a disorder of the dopamine neurotransmitter system; however, this view has not led to new treatments. In this Opinion article, we review the origins of the dopamine theory of addiction and discuss the ability of addictive drugs to elicit the release of dopamine in the human striatum.

There is robust evidence that stimulants increase striatal dopamine levels and some evidence that alcohol may have such an effect, but little evidence, if any, that cannabis and opiates increase dopamine levels.

Moreover, there is good evidence that striatal dopamine receptor availability and dopamine release are diminished in individuals with stimulant or alcohol dependence but not in individuals with opiate, nicotine or cannabis dependence. These observations have implications for understanding reward and treatment responses in various addictions.”

http://www.ncbi.nlm.nih.gov/pubmed/25873042

http://www.thctotalhealthcare.com/category/addiction/

 

Minireview: From the Bench, Toward the Clinic: Therapeutic Opportunities for Cannabinoid Receptor Modulation.

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The effects of cannabinoids have been known for centuries and over the past several decades two G-protein coupled receptors, CB1 and CB2, have been identified that are responsible for their activity.

Endogenous lipid-derived cannabinergic agents have been found, biosynthetic and catabolic machinery characterized, and synthetic agents have been designed to modulate these receptors.

Selective agents including agonists, antagonists, inverse agonists and novel allosteric modulators targeting either CB1 or CB2 have been developed to inhibit or augment their basal tone.

As a result, the role these receptors play in human physiology and their potential therapeutic applications in disease states are being elucidated.

The CB1 receptor while ubiquitous is densely expressed in the brain and CB2 is largely found on cells of immune origin.

This minireview highlights the role of CB1 in excitotoxic assaults in the brain and its potential to limit addiction liability.

In addition, it will examine the relationship between receptor activity and stimulation of insulin release from pancreatic β-cells, insulin resistance and feeding behavior leading toward obesity.

The role of CB2 in the neuropathology of amyotrophic lateral sclerosis and in the central manifestations of chronic HIV infection potentially converges at inflammatory cell activation thereby providing an opportunity for intervention.

Lastly, CB2 modulation is discussed in the context of an experimental model of post-menopausal osteoporosis.

Achieving exquisite receptor selectivity and elucidating the mechanisms underlying receptor inhibition and activation will be essential for the development of the next generation of cannabinergic-based therapeutic agents.”

Role of the endogenous cannabinoid system in nicotine addiction: novel insights.

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“Several lines of evidence have shown that the endogenous cannabinoids are implicated in several neuropsychiatric diseases. Notably, preclinical and human clinical studies have shown a pivotal role of the cannabinoid system in nicotine addiction.

The CB1 receptor inverse agonist/antagonist rimonabant (also known as SR141716) was effective to decrease nicotine-taking and nicotine-seeking in rodents, as well as the elevation of dopamine induced by nicotine in brain reward area. Rimonabant has been shown to improve the ability of smokers to quit smoking in randomized clinical trials. However, rimonabant was removed from the market due to increased risk of psychiatric side-effects observed in humans.

Recently, other components of the endogenous cannabinoid system have been explored. Here, we present the recent advances on the understanding of the role of the different components of the cannabinoid system on nicotine’s effects.

Those recent findings suggest possible alternative ways of modulating the cannabinoid system that could have implication for nicotine dependence treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/25859226

http://www.thctotalhealthcare.com/category/addiction/

Interaction of cannabinoid receptor 2 and social environment modulates chronic alcohol consumption.

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“Genetic and environmental factors contribute nearly with equal power to the development of alcoholism. Environmental factors, like negative life events or emotionally disruptive conditions initiate and promote alcohol drinking and relapse.

The endocannabinoid system is involved in hedonic control and modulates stress reactivity. Furthermore, chronic alcohol drinking alters endocannabinoid signalling, which in turn influences the stress reactivity.

Recently it has been shown that CB2 receptor activity influences stress sensitivity and alcohol drinking. We hypothesised that CB2 receptors influence the impact of environmental risk factors on alcohol preference and consumption. Therefore, in this study we investigated the alcohol-drinking pattern of wild type and CB2 deficient animals under single and group housing conditions using different alcohol drinking models, like forced drinking, intermittent forced drinking and two-bottle choice paradigms.

Our data showed that CB2 receptor modulates alcohol consumption and reward.

Interestingly, we detected that lack of CB2 receptors led to increased alcohol drinking in the intermittent forced drinking paradigm under group housing conditions.

Furthermore, we found that CB2 knockout mice consumed more food and that their body weight gain was modulated by social environment.

On the base of these data, we conclude that social environment critically affects the modulatory function of CB2 receptors especially in alcohol intake.

These findings suggest that a treatment strategy targeting CB2 receptors may have a beneficial effect on pathologic drinking particularly in situations of social stress and discomfort.”

Differential effect of cannabinol and cannabidiol on THC-induced responses during abstinence in morphine-dependent rats.

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“The same dose of cannabinol (CBN) or cannabidiol (CBD) further increased the attenuation of precipitated abstinence signs observed in morphine-dependent rats that also received an acute dose of delta 9-THC. By contrast, rotational behavior (turning), which is observed concomitantly in THC-treated rats during morphine abstinence, was not increased by CBN, but was potentiated by CBD.

These data illustrate differences between psychoinactive cannabinoids in their interaction with delta 9-THC that might be relevant to possible clinical use of Cannabis in narcotic detoxification.”

In Vivo imaging of the cannabinoid CB1 receptor with positron emission tomography.

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“Positron emission tomography (PET) can visualize and quantify receptors and other targets in the living human brain, and recent progress in radioligand development has enabled measurement of cannabinoid CB1 receptors. Cannabinoid CB1 receptors have been implicated in multiple human diseases, such as obesity, mood disorders, and addiction. First in vivo human studies have shown distinctive spatial and temporal alterations in cannabinoid CB1 receptor binding in addictive disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/25788235

Cannabinoid Replacement Therapy (CRT): Nabiximols (Sativex) as a novel treatment for cannabis withdrawal.

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“Cannabis is a common recreational drug that is generally considered to have low addictive potential.

However an increasing number of cannabis users are seeking treatment for dependence on the drug.

There is interest in using agonist (substitution) pharmacotherapies to treat cannabis dependence and here we outline a novel approach involving a buccal spray (Nabiximols) that contains tetrahydrocannabinol (THC) and cannabidiol (CBD).

We review recent research with Nabiximols and highlight findings relevant to clinical practice.”

http://www.ncbi.nlm.nih.gov/pubmed/25777582

Safety and Pharmacokinetics of Oral Cannabidiol When Administered Concomitantly With Intravenous Fentanyl in Humans.

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“Objectives: Cannabidiol (CBD) is hypothesized as a potential treatment for opioid addiction, with safety studies an important first step for medication development. We determined CBD safety and pharmacokinetics when administered concomitantly with a high-potency opioid in healthy subjects.

Conclusions: Cannabidiol does not exacerbate adverse effects associated with intravenous fentanyl administration. Coadministration of CBD and opioids was safe and well tolerated. These data provide the foundation for future studies examining CBD as a potential treatment for opioid abuse.”

http://journals.lww.com/journaladdictionmedicine/Abstract/publishahead/Safety_and_Pharmacokinetics_of_Oral_Cannabidiol.99700.aspx

Individual differences and vulnerability to drug addiction: a focus on the endocannabinoid system.

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“Vulnerability to drug addiction depends upon the interactions between the biological make-up of the individual, the environment, and age. These interactions are complex and difficult to tease apart.

Since dopamine is involved in the rewarding effects of drugs of abuse, it is postulated that innate differences in mesocorticolimbic pathway can influence the response to drug exposure.

In particular, higher and lower expression of dopamine D2 receptors in the ventral striatum (i.e. a marker of dopamine function) have been considered a putative protective and risk factor, respectively, that can influence one’s susceptibility to continued drug abuse as well as the transition to addiction.

This phenomenon, which is phylogenetically preserved, appears to be a compensatory change to increased impulse activity of midbrain dopamine neurons.

Hence, dopamine neuronal excitability plays a fundamental role in the diverse stages of the drug addiction cycle.

In this review, a framework for the evidence that modulation of dopamine neuronal activity plays in the context of vulnerability to drug addiction will be presented.

Furthermore, since endogenous cannabinoids serve as retrograde messengers to shape afferent neuronal activity in a short- and long-lasting fashion, their role in individual differences and vulnerability to drug addiction will be discussed.”

http://www.ncbi.nlm.nih.gov/pubmed/25714966

http://www.thctotalhealthcare.com/category/addiction/

Interactions of the opioid and cannabinoid systems in reward: Insights from knockout studies.

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“The opioid system consists of three receptors, mu, delta, and kappa, which are activated by endogenous opioid peptides (enkephalins, endorphins, and dynorphins).

The endogenous cannabinoid system comprises lipid neuromodulators (endocannabinoids), enzymes for their synthesis and their degradation and two well-characterized receptors, cannabinoid receptors CB1 and CB2.

These systems play a major role in the control of pain as well as in mood regulation, reward processing and the development of addiction.

Both opioid and cannabinoid receptors are coupled to G proteins and are expressed throughout the brain reinforcement circuitry.

A better understanding of opioid-cannabinoid interactions may provide novel strategies for therapies in addicted individuals.”

http://www.ncbi.nlm.nih.gov/pubmed/25698968